T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy but only works in a subset of patients due to the insufficient infiltration, persistent exhaustion, and inactivation of T cells within a tumor. Herein, we develop an engineered probiotic (interleukin [IL]-12 nanoparticle Escherichia coli Nissle 1917 [INP-EcN]) acting as a living drug factory to biosynthesize anti-PD-1 and release IL-12 for initiating systemic antitumor immunity through T cell cascade regulation. Mechanistically, INP-EcN not only continuously biosynthesizes anti-PD-1 for relieving immunosuppression but also effectively cascade promote T cell activation, proliferation, and infiltration via responsive release of IL-12, thus reaching a sufficient activation threshold to ICB. Tumor targeting and colonization of INP-EcNs dramatically increase local drug accumulations, significantly inhibiting tumor growth and metastasis compared to commercial inhibitors. Furthermore, immune profiling reveals that anti-PD-1/IL-12 efficiently cascade promote antitumor effects in a CD8+ T cell-dependent manner, clarifying the immune interaction of ICB and cytokine activation. Ultimately, such engineered probiotics achieve a potential paradigm shift from T cell exhaustion to activation and show considerable promise for antitumor bio-immunotherapy.

Bifidobacterium pseudocatenulatum NCU-08 ameliorated senescence via modulation of the AMPK/Sirt1 signaling pathway and gut microbiota in mice.

Aging is a degenerative disease in which organisms and neurological functions decline. Emerging research has underscored the vital role of the gut microbiota in age-related processes. However, the identification of aging-associated core microbiota remains limited. In this investigation, we isolated a strain of B. pseudocatenulatum NCU-08 from the feces of centenarians and assessed its impact on aging using a mouse model induced by D-gal. Our study revealed the exceptional probiotic attributes of B. pseudocatenulatum NCU-08. Administration of B. pseudocatenulatum NCU-08 significantly ameliorated age-related memory impairment, motor dysfunction, and anxiety-like behaviors in aging mice (p < 0.01). Moreover, tissue staining analysis demonstrated that B. pseudocatenulatum NCU-08 reduced the intensity of SA-ß-gal-positive in the hippocampus of aging mice. It also reversed pathological damage and structural abnormalities in brain and intestinal tissue. B. pseudocatenulatum NCU-08 inhibited neuroinflammation induced by TLR4/NF-κB (p < 0.01) and preserved the blood-brain barrier integrity by activating the AMPK/Sirt1 pathway (p < 0.05). Furthermore, it mitigated neuronal apoptosis and oxidative stress by upregulating the PI3K/AKT signaling pathway (p < 0.01) and enhancing the activities of antioxidant enzymes, including GSH-Px (p < 0.01), SOD (p < 0.01), and CAT (p < 0.01). Besides, analysis of 16S rRNA sequencing data demonstrated that treatment with B. pseudocatenulatum NCU-08 restored intestinal microbiota homeostasis after senescence. It enhanced the abundance of beneficial bacteria while suppressing the growth of pathogenic microorganisms. In summary, our study unveiled that this novel strain of B. pseudocatenulatum NCU-08 exerts anti-aging effects through regulating the AMPK/Sirt1 pathway and intestinal microbiota. It holds promise as a functional food for promoting anti-aging effects and offers a novel approach to address aging and associated metabolic disorders.

Psychobiotics Lactiplantibacillus plantarum JYLP-326: Antidepressant-like effects on CUMS-induced depressed mouse model and alleviation of gut microbiota dysbiosis.

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.

Vaginal microbiota: Potential targets for vulvovaginal candidiasis infection.

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant Candida species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti-Candida effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.

Synergistic Brilliance: Engineered Bacteria and Nanomedicine Unite in Cancer Therapy.

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria-based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine-mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria-mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria-synergized multimodal cancer therapies are highlighted.

Lactobacillus plantarum 24-7 improves postoperative bloating and hard stools by modulating intestinal microbiota in patients with congenital heart disease: a randomized controlled trial.

Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.

VNP20009-Abvec-Igκ-MIIP suppresses ovarian cancer progression by modulating Ras/MEK/ERK signaling pathway.

Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM's apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: • This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins • The engineered bacteria can target and colonize tumor sites in vivo • VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.

Therapeutic Evaluation of Bifidobacterium animalis subsp. lactis MH-02 as an Adjunctive Treatment in Patients with Reflux Esophagitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

Proton pump inhibitors (PPIs) are currently routinely used for the treatment of reflux esophagitis (RE); however, with frequent symptom recurrence after discontinuation and limited clinical improvement in accompanying gastrointestinal symptoms. This study aims to explore the adjuvant therapeutic effect of Bifidobacterium supplement for RE patients. A total of 110 eligible RE patients were recruited and randomly assigned to the placebo and probiotic groups. All patients were treated with rabeprazole tablets and simultaneously received either Bifidobacterium animalis subsp. lactis MH-02 or placebo for 8 weeks. Patients who achieved clinical remission then entered the next 12 weeks of follow-up. RDQ, GSRS scores, and endoscopy were performed to assess clinical improvement, and changes in intestinal microbiota were analyzed with high-throughput sequencing. Our results revealed that MH-02 combined therapy demonstrated an earlier time to symptom resolution (50.98% vs. 30.61%, p = 0.044), a significant reduction in the GSRS score (p = 0.0007), and a longer mean time to relapse (p = 0.0013). In addition, high-throughput analyses showed that MH-02 combined therapy increased the α (p = 0.001) diversity of gut microbiota and altered microbial composition by beta diversity analysis, accompanied with significantly altered gut microbiota taxa at the genus level, where the abundance of some microbial genera including Bifidobacterium, Clostridium, and Blautia were increased, while the relative abundance of Streptococcus and Rothia were decreased (p < 0.05). Collectively, these results support the beneficial effects of MH-02 as a novel complementary strategy in RE routine treatment.

Vaginal extracellular vesicles impair fertility in endometriosis by favoring Th17/Treg imbalance and inhibiting sperm activity.

Extracellular vesicles (EVs) play a key role in various diseases. However, their effect on endometriosis (EMs)-associated infertility is poorly understood. We co-cultured EVs from the female vaginal secretions with human sperm and also generated a mouse model of EMs by allogenic transplant to explore the effect of EVs on fertility. EVs from individuals with EMs-associated infertility (E-EVs) significantly inhibited the total motility (26.46% vs. 47.1%), progressive motility (18.78% vs. 41.06%), linear velocity (21.98 vs. 41.91 µm/s) and the acrosome reaction (AR) rate (5% vs. 22.3%) of human sperm in contrast to the control group (PBS). Furthermore, E-EVs dose-dependently decreased the intracellular Ca2+ ([Ca2+]i), a pivotal regulator of sperm function. Conversely, healthy women (H-EVs) increased human sperm motion parameters, the AR rate, and sperm [Ca2+]i. Importantly, the mouse model of EMs confirmed that E-EVs further decreased the conception rate and the mean number of embryo implantations (7.6 ± 3.06 vs. 4.5 ± 3.21) compared with the control mice by inducing the production of inflammatory cytokines leading to a Th17/Treg imbalance. H-EVs could restore impaired fertility by restoring the Th17/Treg balance. We determined the impact of EVs derived from the female genital tract on human sperm function and studied the possible mechanisms by which it affects fertility. Our findings provide a novel rationale to ameliorate EMs-associated infertility.

Bifidobacterium longum SX-1326 ameliorates gastrointestinal toxicity after irinotecan chemotherapy via modulating the P53 signaling pathway and brain-gut axis.

BACKGROUND: Colorectal cancer (CRC) is a prevalent malignant malignancy affecting the gastrointestinal tract that is usually treated clinically with chemotherapeutic agents, whereas chemotherapeutic agents can cause severe gastrointestinal toxicity, which brings great pain to patients. Therefore, finding effective adjuvant agents for chemotherapy is crucial. METHODS: In this study, a CRC mouse model was successfully constructed using AOM/DSS, and the treatment was carried out by probiotic Bifidobacterium longum SX-1326 (B. longum SX-1326) in combination with irinotecan. Combining with various techniques of modern biomedical research, such as Hematoxylin and Eosin (H&E), Immunohistochemistry (IHC), Western blotting and 16S rDNA sequencing, we intend to elucidate the effect and mechanism of B. longum SX-1326 in improving the anticancer efficacy and reducing the side effects on the different levels of molecules, animals, and bacteria. RESULTS: Our results showed that B. longum SX-1326 enhanced the expression of Cleaved Caspase-3 (M vs. U = p < 0.01) and down-regulated the expression level of B-cell lymphoma-2 (Bcl-2) through up-regulation of the p53 signaling pathway in CRC mice, which resulted in an adjuvant effect on the treatment of CRC with irinotecan. Moreover, B. longum SX-1326 was also able to regulate the gut-brain-axis (GBA) by restoring damaged enterochromaffin cells, reducing the release of 5-hydroxytryptamine (5-HT) in brain tissue (I vs. U = 89.26 vs. 75.03, p < 0.05), and further alleviating the adverse effects of nausea and vomiting. In addition, B. longum SX-1326 reversed dysbiosis in CRC model mice by increasing the levels of Dehalobacterium, Ruminnococcus, and Mucispirillum. And further alleviated colorectal inflammation by downregulating the TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: In conclusion, our work reveals that B. longum SX-1326 has a favorable effect in adjuvant irinotecan for CRC and amelioration of post-chemotherapy side effects, and also provides the theoretical basis and data for finding a safe and efficient chemotherapeutic adjuvant.

The intestinal microbiota exerts a sex-specific influence on neuroinflammation in a Parkinson's disease mouse model.

Parkinson's disease (PD) is a neurodegenerative disorder characterised by chronic and progressive symptoms; it is more prevalent in men than in women. The sex-specific influence of the intestinal microbiota has been associated with some neurodegenerative diseases, but the relationship with PD is currently unclear. In this study, we treated mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish a PD mouse model, and we utilised an antibiotic cocktail (Abx) to deplete the intestinal microbiota to evaluate the influence of the intestinal microbiota on male and female PD mice. MPTP treatment obviously caused bradykinesia and low mobility in female and male mice. Meanwhile, Abx treatment exerted a greater effect on male mice than female mice. Western blotting and immunofluorescence revealed that male mice treated with MPTP had higher expression of α-synuclein and proteins related to neuroinflammation and intestinal inflammation based on activation of glial cells and the TLR4-MyD88 signalling pathway. The sex-specific differences could be due to the different composition of the intestinal microbiota. Specifically, female mice had significantly higher abundance of Allobaculum, Turicibacter and Ruminococcus than male mice. Moreover, the abundance of the probiotic genus Bifidobacterium showed opposite trends in male and female mice. Our results indicate that the intestinal microbiota has an important effect on PD mice, especially male mice, by influencing neuroinflammation through the microbiota-gut-brain axis. In the future, there should be a focus on providing more reliable evidence for the pathogenesis and precise treatment of PD.

Lactobacillus acidophilus JYLA-126 Ameliorates Obesity-Associated Metabolic Disorders by Positively Regulating the AMPK Signaling Pathway Through the Gut-Liver Axis.

Obesity is a chronic metabolic disease worldwide and is considered a major health problem in contemporary society. Lactobacillus acidophilus have demonstrated beneficial effects on obesity, but the specific mechanism of how it exerts beneficial effects has not been elucidated. Here, we found that L. acidophilus JYLA-126 had good biological properties for intestinal health, such as antioxidation, acid tolerance, bile salt tolerance, antimicrobial activity, and gut colonization. We further identified that supplementation of L. acidophilus JYLA-126 obese mice possessed a dose-dependent amelioration of body weight, intestinal imbalance, and metabolic disorders compared to HFD-induced mice. Mechanistically, the excellent slimming effect of L. acidophilus JYLA-126 was achieved mainly by reversing HFD-induced gut dysbiosis, inhibiting inflammatory factors and balancing the homeostasis of the gut-liver axis. Specifically, L. acidophilus JYLA-126 improved hepatic glycogen synthesis, lowered oxidative stress, and facilitated lipid metabolism by regulating AMPK signaling pathway-related protein expression to restore the overall metabolic level. Accordingly, L. acidophilus JYLA-126 promoted energy uptake efficiency in obese mice, resulting in significant expression of uncoupling protein 1 (UCP1) protein in brown adipose tissue (BAT), and markedly reduced the size of adipocytes. These findings indicate that the anti-obesity activity of L. acidophilus JYLA-126 correlates with activation of the AMPK signaling pathway through improved gut-liver interactions.

Dapagliflozin promotes angiogenesis in hindlimb ischemia mice by inducing M2 macrophage polarization.

Critical limb ischemia (CLI) is associated with a higher risk of limb amputation and cardiovascular death. Dapagliflozin has shown great potential in the treatment of cardiovascular disease. However, the effects of dapagliflozin on CLI and the underlying mechanisms have not been fully elucidated. We evaluated the effect of dapagliflozin on recovery from limb ischemia using a mouse model of hindlimb ischemia. The flow of perfusion was evaluated using a laser Doppler system. Tissue response was assessed by analyzing capillary density, arterial density, and the degree of fibrosis in the gastrocnemius muscle. Immunofluorescence and Western blot were used to detect the expression of macrophage polarization markers and inflammatory factors. Our findings demonstrate the significant impact of dapagliflozin on the acceleration of blood flow recovery in a hindlimb ischemia mouse model, concomitant with a notable reduction in limb necrosis. Histological analysis revealed that dapagliflozin administration augmented the expression of key angiogenic markers, specifically CD31 and α-SMA, while concurrently mitigating muscle fibrosis. Furthermore, our investigation unveiled dapagliflozin's ability to induce a phenotypic shift of macrophages from M1 to M2, thereby diminishing the expression of inflammatory factors, including IL-1ß, IL-6, and TNF-α. These effects were partially mediated through modulation of the NF-κB signaling pathway. Lastly, we observed that endothelial cell proliferation, migration, and tube-forming function are enhanced in vitro by utilizing a macrophage-conditioned medium derived from dapagliflozin treatment. Taken together, our study provides evidence that dapagliflozin holds potential as an efficacious therapeutic intervention in managing CLI by stimulating angiogenesis, thereby offering a novel option for clinical CLI treatment.

Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.

Neuroprotective effects of an engineered Escherichia coli Nissle 1917 on Parkinson's disease in mice by delivering GLP-1 and modulating gut microbiota.

Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon-like peptide-1 (GLP-1). However, the extremely short half-life of GLP-1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN-GLP-1 that effectively delivers the heterologous GLP-1 molecule. Subsequently, we assessed its neuroprotective effects on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. We demonstrated that EcN-GLP-1 treatment could improve motor deficits, increase tyrosine hydroxylase-positive neurons, suppress microglia and astrocyte activation, reduce brain and colon inflammation, and ameliorate colonic barrier function damaged by MPTP induction. Meanwhile, we confirmed that the oral administration of EcN-GLP-1 could restore the disturbance of gut microbiota in the MPTP-induced PD mice, by reducing the relative abundances of Akkermansia and Oscillospira, and increasing the level of Prevotella in the gut. These results support further development of an engineered probiotic platform in which production of GLP-1 for gut-brain disorders, such as PD.

Positive efficacy of Lactiplantibacillus plantarum MH-301 as a postoperative adjunct to endoscopic sclerotherapy for internal hemorrhoids: a randomized, double-blind, placebo-controlled trial.

Background: Endoscopic sclerotherapy is a widely used minimally invasive procedure for internal hemorrhoids, yet postoperative symptoms remain a concern. The purpose of this study is to investigate the postoperative adjuvant efficacy of Lactiplantibacillus plantarum. Method: In this study, patients (≥18 years) with internal hemorrhoids that conformed to Goligher's classification of grade I-III received administration of L. plantarum MH-301 for 4 weeks following endoscopic sclerotherapy. The primary clinical endpoint in this study was the improvement rate, which was defined as the percentage of patients whose n-HDSS score decreased to 0 following the procedure. Stools were collected for high-throughput sequencing analysis post operation. Result: A total of 103 participants (51 in the LP group and 52 in the C group) were recruited, with 96 completing the entire trial (49 in the LP group and 47 in the C group). The primary clinical endpoint showed a higher improvement rate in the LP group (87.8% vs. 70.2%, P = 0.045). High-throughput sequencing analysis demonstrated that the LP group had a greater diversity of intestinal microbiota and a higher relative abundance of beneficial bacteria such as Bifidobacterium, Megamonas, and Lactobacillus. No significant difference in postoperative complications and adverse events was found. Conclusion: This paper concludes that the administration of L. plantarum MH-301 after endoscopic sclerotherapy can further increase the efficacy of the procedure and improve bowel movements. Regulation of intestinal microbiota may be the potential mechanism for the efficacy of L. plantarum MH-301.

Combination of thalidomide and Clostridium butyricum relieves chemotherapy-induced nausea and vomiting via gut microbiota and vagus nerve activity modulation.

Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and Clostridium butyricum. Our results suggested that the combination of THD and C. butyricum abundantly enhanced the anticancer effect of cisplatin via activating the caspase-3 apoptosis pathway, and also ameliorated CINV via inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HT3R and NK-1R) in brain and colon. Additionally, the combination of THD and C. butyricum reversed the gut dysbacteriosis in CRC mice by increasing the abundance of Clostridium, Lactobacillus, Bifidobacterium, and Ruminococcus at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1ß, and TNF-α. In all, these results suggest that the combination of THD and C. butyricum had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.

Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer via regulating Hedgehog signaling pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, which remains a threat to female health at all ages. Hypotheses for EOC development include the continuous presence of inflammation, in which microbiota and inflammatory cytokines participate in cancer-related signaling pathway activation. Hedgehog (Hh) signaling is prominent for EOC progression, and interacts with inflammation response related to gut microbiota (GM). However, the precise roles of GM during this process are unknown. Here, we showed that the GM from patients with EOC differed from that of healthy women and had GM dysbiosis. We found that EOC modeling may lead to GM changes in mice, and it restored after the administration of GM from healthy controls, while GM from patients with EOC further exacerbated GM dysbiosis. Furthermore, we found that GM from EOC markedly promoted tumor progression and activated Hh signaling; meanwhile, it increased the extent of inflammation and activated NF-κB signaling, but GM from healthy controls improved them. Our results demonstrate how GM dysbiosis promoted EOC progression by activating Hh signaling mediated by TLR4/NF-κB signaling. We anticipate our assay to be a new thought for exploring the role of GM in EOC development. Furthermore, improving GM dysbiosis is a novel therapeutic approach for delaying EOC development.